rs1044129

chr15-33866065-A-Gchr15-33866065-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001036.6(RYR3):c.*839A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.615 in 154,892 control chromosomes in the GnomAD database, including 31,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (30745 hom., cov: 32)
  • Exomes 𝑓: 0.73 (782 hom.)
• Consequence: RYR3 NM_001036.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.91

Genes affected

RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 15-33866065-A-G is Benign according to our data. Variant chr15-33866065-A-G is described in ClinVar as [Benign]. Clinvar id is 706987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR3	NM_001036.6	c.*839A>G		3_prime_UTR_variant	104/104	ENST00000634891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR3	ENST00000634891.2	c.*839A>G		3_prime_UTR_variant	104/104	1	NM_001036.6	P4

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93121 AN: 151898 Hom.: 30745 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.726 AC: 2086 AN: 2874 Hom.: 782 Cov.: 0 AF XY: 0.723 AC XY: 1114 AN XY: 1540

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.746

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.731

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.613 AC: 93135 AN: 152018 Hom.: 30745 Cov.: 32 AF XY: 0.613 AC XY: 45542 AN XY: 74318

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.625

Alfa AF: 0.711 Hom.: 64352

Bravo AF: 0.600

Asia WGS AF: 0.497 AC: 1729 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 08, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	14
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1044129; hg19: chr15-34158266; COSMIC: COSV60734207; COSMIC: COSV60734207;